論文 - 詳細
| RRC ID | 57225 |
|---|---|
| 著者 | Colmenares SU, Swenson JM, Langley SA, Kennedy C, Costes SV, Karpen GH. |
| タイトル | Drosophila Histone Demethylase KDM4A Has Enzymatic and Non-enzymatic Roles in Controlling Heterochromatin Integrity. |
| ジャーナル | Dev Cell |
| Abstract |
Eukaryotic genomes are broadly divided between gene-rich euchromatin and the highly repetitive heterochromatin domain, which is enriched for proteins critical for genome stability and transcriptional silencing. This study shows that Drosophila KDM4A (dKDM4A), previously characterized as a euchromatic histone H3 K36 demethylase and transcriptional regulator, predominantly localizes to heterochromatin and regulates heterochromatin position-effect variegation (PEV), organization of repetitive DNAs, and DNA repair. We demonstrate that dKDM4A demethylase activity is dispensable for PEV. In contrast, dKDM4A enzymatic activity is required to relocate heterochromatic double-strand breaks outside the domain, as well as for organismal survival when DNA repair is compromised. Finally, DNA damage triggers dKDM4A-dependent changes in the levels of H3K56me3, suggesting that dKDM4A demethylates this heterochromatic mark to facilitate repair. We conclude that dKDM4A, in addition to its previously characterized role in euchromatin, utilizes both enzymatic and structural mechanisms to regulate heterochromatin organization and functions. |
| 巻・号 | 42(2) |
| ページ | 156-169.e5 |
| 公開日 | 2017-7-24 |
| DOI | 10.1016/j.devcel.2017.06.014 |
| PII | S1534-5807(17)30502-6 |
| PMID | 28743002 |
| PMC | PMC5572651 |
| MeSH | Animals Biocatalysis Cell Cycle / genetics Cell Cycle Checkpoints / genetics Chromosomal Position Effects / genetics DNA Breaks, Double-Stranded DNA Repair / genetics Drosophila Proteins / chemistry Drosophila Proteins / metabolism* Drosophila melanogaster / cytology* Drosophila melanogaster / enzymology* Drosophila melanogaster / genetics Fertility / genetics Gene Expression Regulation Gene Silencing Heterochromatin / metabolism* Histone Demethylases / metabolism* Histones / metabolism Lysine / metabolism Methylation Mutation / genetics Protein Domains Transcription, Genetic |
| IF | 9.19 |
| 引用数 | 17 |
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 11 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
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